Obesity is the most common disorder of the developed world. The ready availability of food in most areas, a shift to relatively sedentary lifestyles, and changing food sources have contributed to this problem.
Researchers have hypothesized that recent changes in food sources have led to an imbalance in the optimal ratio of fatty acid intake. These imbalances may influence obesity. Specifically, modern diets have increased amounts of omega-6 fatty acids as compared to omega-3 fatty acids, as noted in Simopoulos, "Evolutionary Aspects of Diet: Fatty Acids, Insulin Resistance and Obesity", in Obesity: New Directions in Assessment and Management, VanItallie and Simonpoulos ed., The Charles Press, Philadelphia, 241-61 (1995). Omega-6 fatty acids are represented by linoleic acid and omega-3 fatty acids are represented by alpha-linolenic acid. A balance between omega-6 and omega-3 fatty acids existed for most of human history and has now been changed to a ratio of about 20 to 25:1 in the favor of omega-6 fatty acids. This increase in omega-6 fatty acids is due the increased intake of vegetable oils and increased amounts saturated and monounsaturated fatty acids (depot fat) in domestic meat as compared to meat from wild game. The replacement of saturated fats with unsaturated fats has been widely recommended, resulting in increased intake of omega-6 fatty acids from vegetable oils and trans fatty acids from margarine. This means that humans have been exposed to pharmacological doses of omega-6 fatty acids from the first time in their evolutionary history.
Trans fatty acids are rarely found in nature and are produced by the hydrogenation of vegetable oils. Studies indicate that uncommon isomers of polyunsaturated fatty acids and trans fatty acids interfere with normal omega-3 and omega-6 fatty acid metabolism, inducing significant partial deficiencies of omega-3 and omega-6 essential fatty acids, as suggested by Holman et al., Proc. Nat. Acad. Sci. USA 88:4830-34 (1991). Further evidence of disturbed omega-6 metabolism associated with obesity has been obtained from the Zucker rat model, and correlated to humans and multiloci obese mouse models. Feeding studies showed that animals gavaged with gamma linoleic acid (18:3w6) exhibited reduced food intake and reduced weight gain with return of liver arachidonic acid levels to normal. (Sere VanItallie, supra, p. 82 et seq.). Since linoleic acid is an essential precursor in the biosynthesis of arachidonic acid, the correlation of an increase in the latter by gavage of the former is a predictable outcome. However, a careful analysis of the metabolites of these fatty acids demonstrates that obesity is correlated to an accelerated systemic 20:4w6 flux (a loop of transport of 20:4w6 from liver to peripheral membranes and return to the liver via LDL/HDL, rather than to impairment in arachidonic acid production per se).
The significance of changes in the fatty acid content of the diet over time is unclear. Some researchers have recommended restriction in the diet of food containing unusual isomeric unsaturated fatty acids, and substitution of oils having a high level of omega-3 linoleic acid compared to omega-6 linoleic acid. See, for example, Holman, et al., PNAS, 88: 4830 (1991). Whether the shifts in diet are truly responsible for the rise in obesity will probably not be known until large scale, long term double blinded clinical trials have been conducted.
It is clear that the phenomenon of obesity is an exceedingly complex biochemical condition. From a physiological standpoint, obesity is no less complex. The utilization of food energy involves three pathways. The basal or resting metabolic rate is the rate at which energy is expended simply to maintain the body intact, and constitutes approximately 70 percent of energy utilization in the average sedentary individual. Another 10 percent of energy is heat generated by the digestion and processing of food. Finally, about 20 percent of food energy is consumed during physical activity.
The allocation of these energy utilizations has some very interesting effects. For example, when an obese individual is subjected to food restriction, the body's reaction is to dramatically reduce basal metabolism. Thus, the weight loss from diet restriction is always less than the loss predicted from the caloric deficit, resulting in substantial deviation from the Kleiber curve. (For a detailed discussion of energy management and the evidence of physiological regulation, see Stunkard and Wadden, eds., Obesity: Theory and Therapy, 2nd ed., Raven Press: 1993). As the body gains weight, both the number of adipocytes and their lipid content increases. During food restriction, basal metabolism declines, and the lipid content, but not cell numbers of adipocytes decrease. When caloric load is resumed, most of the food energy is directed into lipogenesis (to restore the obese weight set point), and there is a great excess of lipid depleted lipocytes available to absorb the new lipids. This explains why dieters tend to gain weight rapidly after discontinuing a fat-restricted diet.
Apart from diet, several methods of chemically treating obesity with pharmacologically active substances have been identified. However, these methods involve certain risk. Caffeine and amphetamine based diet aids may be addictive and adversely affect other areas of health. The combination of fenfluramine and phentermine has been proven to cause heart valve disease. Other dietary aids are available over the counter. Almost all of these chemical remedies have as their objective, weight loss through reduced food intake, brought about by appetite suppression. The ideal treatment for obesity would achieve weight reduction through a safe intervention--the natural biochemical and physiological processes which direct food into tissue mass.